Importance of HLA-DRBI and DQA1 genes and the amino acid polymorphisms in the functional domain of DRBI chain in multiple slerosis

Abstract

The association of some HLA class II alleles with multiple sclerosis (MS) has been amply documented. In the present study the role of HLA class II haplotypes and genotypes and of polymorphic amino acids at the DR/S1 locus, located in the antigen binding groove and the CD4 binding domain of the DRβ1 chain, were studied in 78 unrelated Caucasian chronic progressive MS (CP MS) patients and 204 controls. The results confirmed the positive association of the DRB1 * 1501 allele and through linkage also of the DRB1 * 1501-DQA1 *0102 haplotype with MS. In addition, the results showed that the DRB1 * 1501/DRB1 *0400 or DRβ1Ala 71 + His13+ genotype conferred the highest relative risk for MS (RR = 9.14). Alleles encoding for DRβ1phe47+, DRβ1Asp70+ and DRβ1Thr140+, DQα1phe25+, DQα1Leu69+ residues were protective and the highest protection (RR = 0.24) was provided by the DRβ1phe47+-DQα1phe25 + and DRβ1Ser13+-DQα1phe25+ haplotypes. Our results suggest that both DQ and DR αβ heterodimers might contribute to the increased or decreased risk to develop MS by the shape of their antigen-binding groove.